On board was the largest flight crew for a manned space mission up to that time: Mission Commander John W. Young (Captain, United States Navy, Retired), Pilot; Lieutenant Colonel Brewster H. Shaw, Jr., United States Air Force; Mission Specialists Owen K. Garriott, Ph.D., and Robert A.R. Parker, Ph.D.; and Payload Specialists Ulf Dietrich Merbold, Dr. rer. nat, of the European Space Agency (ESA); and Lieutenant Colonel Byron K. Lichtenberg, D.Sc., USAF (Massachusetts Air National Guard).

Columbia carried the NASA/ESA Spacelab module in the cargo bay. The mission was primarily to carry out 72 scientific experiments in astronomy, physics, biology, as well as to make observations of the Earth.